Estradiol and Elagolix for Menopause

Overseen By Olivia K. Leach, MS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Penn State University

Must not be taking: Hormone therapy, Hormonal contraceptives

Disqualifiers: Chron's, Diverticulitis, Tobacco, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 3 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how estrogen affects the body's ability to handle heat stress, particularly in women approaching or experiencing menopause. Researchers are testing the impact of an estradiol patch (a form of hormone therapy) and a medication called Elagolix to observe their influence on heat responses. Women aged 42 to 64 who do not use hormone treatments and do not smoke may be suitable candidates. The study investigates whether adding or reducing estrogen can alleviate heat-related health issues. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, and this research seeks to understand how it benefits more patients.

Do I need to stop my current medications for the trial?

The trial requires that participants are not using hormone therapy or hormonal contraceptives, so you would need to stop these medications if you are currently taking them.

What is the safety track record for Estradiol and Elagolix?

Research has shown that the estradiol patch, used for hormone therapy, is generally safe for most women. It is approved for treating menopause symptoms and preventing bone weakening in postmenopausal women. Recent studies have even led to the removal of previous warning labels about serious risks like breast cancer or heart attacks, suggesting increased confidence in its safety.

Elagolix is a medication often used to manage pain from endometriosis. While patients have generally tolerated it well, some have experienced side effects like headaches and hot flashes. Various studies have tested both treatments to ensure their safety.

Overall, past research indicates that both the estradiol patch and Elagolix are well-tolerated, with clear guidelines to monitor any side effects. Participants considering the trial can feel reassured by the existing safety evidence for these treatments. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for menopause because they offer innovative approaches to managing hormonal changes. The use of an estradiol patch provides a transdermal delivery method, which can offer a steadier release of hormones compared to oral therapies. This might reduce the risk of certain side effects associated with fluctuating hormone levels. Additionally, Elagolix, typically used for endometriosis, is being explored for its potential to suppress estrogen in premenopausal women, providing a novel mechanism of action not common in current menopause treatments. These approaches could offer new options for symptom management and hormone regulation.

What evidence suggests that this trial's treatments could be effective for menopause-related heat stress?

Research has shown that estradiol patches, one of the treatments in this trial, can effectively relieve menopausal symptoms, often within two weeks of starting treatment. They help maintain balanced hormone levels, which is crucial for managing the body's heat regulation. Studies have found that estradiol is particularly effective at maintaining bone strength and reducing hot flashes.

Elagolix, another treatment option in this trial, lowers certain hormones and has proven effective in reducing endometriosis pain. Although primarily used for endometriosis, its hormone-lowering ability might also aid in managing the body's heat response. Both treatments in this trial aim to balance hormones, which is essential for managing menopause symptoms and potentially reducing heat-related health risks. ^{6 7 8 9 10}

Who Is on the Research Team?

W. Larry Kenney, Ph.D.

Principal Investigator

The Pennsylvania State University

Are You a Good Fit for This Trial?

This trial is for postmenopausal women over the age of 65 who are experiencing issues with body temperature regulation. Participants should not have any conditions that could interfere with hormone therapy or thermoregulation studies.

Inclusion Criteria

I am a woman aged between 42 and 64.

Exclusion Criteria

High-risk determined by the Atherosclerotic Cardiovascular Disease (CVD) Risk Factor Assessment

I am currently on hormone therapy.

Abnormal resting exercise electrocardiogram (ECG)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Premenopausal women receive a GnRH antagonist to reduce estrogen, and postmenopausal women receive a transdermal estradiol patch to increase estrogen.

3 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol patch

Trial Overview The study tests how estrogen affects body heat management in older women. It involves an estradiol patch, which provides estrogen, and Elagolix Oral Tablet to counteract it, compared against placebo counterparts in a controlled environment.

How Is the Trial Designed?

Group I: Premenopausal estrogen suppression Experimental Treatment 2 Interventions

Participants take a cellulose placebo tablet for 4 days prior to baseline testing and continue until experimental visits are complete. Following completion of placebo testing, participants begin taking 400 mg/day Elagolix for 4 days prior to testing and continue until experimental visits are complete.

Group II: Postmenopausal estrogen supplementation Experimental Treatment 2 Interventions

Participants wear a transdermal estradiol patch or placebo patch for 5 days prior to testing and continue until experimental visits are complete. After 48 hr washout, participants then wear the alternative treatment for 5 days prior to testing until experimental visits are complete.

Who Is Running the Clinical Trial?

Penn State University

Lead Sponsor

Trials

380

Recruited

131,000+

Published Research Related to This Trial

The Women's Health Initiative (WHI) study raised safety concerns about hormone therapy, particularly focusing on a specific oral regimen of conjugated equine estrogen and medroxyprogesterone, which may not represent the broader population's response to hormone therapy.

In contrast, the once-weekly transdermal patch delivering 17beta-estradiol and levonorgestrel has been shown to effectively reduce vasomotor symptoms and improve quality of life without adverse effects like endometrial hyperplasia or negative impacts on cholesterol, making it a safer alternative for managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

17Beta-estradiol/levonorgestrel transdermal system for the management of the symptomatic menopausal woman. Shulman, LP.[2019]

In a study of 166 postmenopausal women, both a transdermal 17 beta-estradiol patch and oral estrogen therapy significantly reduced the average number of hot flashes from 6 per day to 1 per day over 12 weeks, showing similar efficacy between the two treatments.

The transdermal patch was associated with a greater reduction in other symptoms like sweating and difficulty concentrating, and had fewer skin-related side effects compared to oral estrogen, indicating it may be a safer alternative for managing postmenopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of transdermal with oral hormone substitution: a multicenter study with a new matrix patch]. Sajtos, B., Herold, J., Winkler, UH., et al.[2013]

The new 7-day estrogen matrix patch (Climara) effectively alleviates climacteric symptoms in postmenopausal women, showing positive results in two 11-week placebo-controlled studies with good tolerance across different doses.

The 7-day patch demonstrated superior adhesion compared to the Estraderm patch, and absorption of estradiol was found to be higher and more consistent when applied to the buttock rather than the abdomen, indicating potential for optimized application sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a 7-day estrogen patch: principles and practice. Notelovitz, M.[2013]

The seven-day transdermal estradiol patch significantly reduced menopausal symptoms over six months, as indicated by a decrease in the average climacteric score from 27.18 at admission to 12.18 by the end of the study.

The patch demonstrated excellent adhesion with over 94% remaining securely in place, and it was generally well tolerated, with skin irritation being the most common side effect, primarily itching.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and acceptability of a seven-day, transdermal estradiol patch for estrogen replacement therapy. Jarupanich, T., Lamlertkittikul, S., Chandeying, V.[2013]

In a study of 121 menopausal women using transdermal oestradiol patches for 3 months to 2.5 years, the patches were found to be effective in relieving menopausal symptoms, with most women preferring them over oral therapy.

The patches were generally well tolerated, with few side effects reported; however, some women experienced minor issues like breast tenderness and weight gain, and there were challenges with patch adhesiveness during hot weather.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Australian experience of transdermal oestradiol patches in a subtropical climate. O'Neill, S., Kirkegard, Y.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7901127/

An Evidence-Based Review of Elagolix for the Treatment of ... Studies up to 12 months long showed continued efficacy and reduction in dysmenorrhea of up to 75%, with 50%–60% reduction in non-menstrual pain. Elagolix was ...

2. ajog.org ajog.org/article/S0002-9378(24)00731-2/fulltext

Efficacy, tolerability, and bone density outcomes of elagolix ... The results from the current study indicate that endometriosis-associated pain treatment with ELA+AB therapy provides efficacious reductions in ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1700089

Treatment of Endometriosis-Associated Pain with Elagolix, ... Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women ...

4. academic.oup.com academic.oup.com/jcem/article/102/5/1683/3001063

Dose-Dependent Suppression of Gonadotropins and Ovarian ... As in the previous study (13), administration of elagolix led to more pronounced suppression of LH than FSH, as evidenced by sustained suppression of LH in all ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666334123000375

The role of elagolix in the suppression of ovulation in donor ... These data suggest that elagolix binds quickly and effectively to the GnRH receptor, but suppression was reversed rapidly after discontinuation.

6. mayoclinic.org mayoclinic.org/drugs-supplements/estradiol-transdermal-route/description/drg-20075306

Estradiol (transdermal route) - Side effects & dosage Estradiol transdermal gel, patch, and spray are used to treat moderate to severe symptoms of menopause (eg, feelings of warmth in the face, neck, and chest)

7. statnews.com statnews.com/2025/11/10/fda-reverses-hormone-warning-menopause-health/

FDA ends hormone therapy warning, says safe ... - STAT News FDA removes black box warning on hormone therapy, reflecting new science on menopause, heart health, and evolving views on women's care.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/206685Orig1s000Lbl.pdf

This label may not be the latest approved by FDA. For current ... Estradiol transdermal system (twice-weekly) is indicated for the prevention of postmenopausal osteoporosis. When prescribing solely for the prevention of ...

9. nbcnews.com nbcnews.com/health/womens-health/hormone-replacement-therapy-no-warning-label-fda-rcna243008

Hormone replacement therapy will no longer carry a ... Hormone therapies for menopause will no longer carry a black box warning about serious risks such as breast cancer, heart attack and stroke, ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35357370/

Transdermal estrogen therapy in menopausal women at ... This scoping review provides data regarding the safety of transdermal MHT use in postmenopausal women with risk factors for VTE, and clinicians ...